A recent large-scale study has revealed that Herpes simplex virus 1 (HSV-1), which is most commonly known for causing cold sores, may considerably increase the risk of Alzheimer’s disease. Scientists discovered that those with HSV-1 had an 80% higher risk of Alzheimer’s, whereas those receiving antiviral drugs had a 17% lower risk.
The number of people with Alzheimer’s disease in the US is rapidly increasing. According to statistics, about 7 million Americans have Alzheimer’s, and by 2050, that figure is expected to rise to approximately 13 million [1]. This debilitating neurodegenerative disorder cost the nation over $300 billion in 2020 [2].
However, despite its impact and extensive research to uncover its exact cause and treatment, we still don’t fully understand what causes it.
In Alzheimer’s disease, toxic tau tangles and accumulating amyloid-beta plaques are two specific brain pathologies. The possibility that infections could be involved is one theory that has been gaining traction. Although the exact cause of Alzheimer’s is unknown, some research has suggested that the common cold sore virus, HSV-1, may have a role by triggering a persistent infection in the brain that results in inflammation and neurodegeneration.
One of the first to demonstrate the presence of HSV-1 DNA in the typical Alzheimer’s brain plaques was Professor Ruth Itzhaki in the 1990s [3]. Her team also discovered that the virus can cause neuronal damage similar to Alzheimer’s, particularly in those who have the genetic risk factor APOE ε4.
About three decades later, new research is supporting her conclusions. The evidence suggests that HSV-1 may contribute to amyloid-beta (Aβ) accumulation, leading to the formation of plaques in the brain [4].
However, extensive, real-world data has been lacking. The new research examined insurance records to find evidence that HSV-1 may increase Alzheimer’s risk and to see if antiviral medications can lower that risk [5]. BMJ Open published the research findings.
What is HSV-1?
Herpes simplex virus type 1 (HSV-1) is a widespread virus. Since it is a neurotropic virus, it can infect nerve cells, which are responsible for transmitting and receiving signals to and from the brain. According to WHO estimates, about 64% of people under 50 worldwide carry this virus, frequently without realizing it [6]. Some people may experience cold sores as a result of its reactivation, while others may experience different effects.
An early infection may trigger mild to severe symptoms, such as fever, headache, and muscle pain, as well as blisters and ulcers around the mouth or lips.
After that, HSV-1 normally remains latent in the nervous system, occasionally reactivating in response to stress or disease. Symptoms like cold sores can occur during reactivation; however, many people do not experience any symptoms.
What did the new research investigate?
Adding to the growing body of data, a recent study conducted by Gilead Sciences Inc., an American biopharmaceutical company, and the University of Washington’s Department of Medicine (UW Medicine) found a link between the risk of Alzheimer’s disease and herpes simplex virus type 1 (HSV-1). Furthermore, scientists discovered that taking antiviral drugs following a diagnosis can lower that risk [5].
Researchers utilized data from the IQVIA PharMetrics Plus claims database, which contains medical and pharmacy claims information for over 215 million individuals in the United States. They identified 344,628 patients over the age of 50 who were diagnosed with Alzheimer’s disease or other dementias similar to Alzheimer’s between 2006 and 2021. They paired every individual with a control who had never had any neurological conditions based on factors such as age, sex, and geographic region.
Then, the team examined how many people had previously been diagnosed with HSV-1 and if they had received antiviral drug treatment for the condition. .
Compared to 0.24% of controls, 0.44% of individuals with Alzheimer’s had a prior HSV-1 diagnosis. After adjusting for various influencing factors, the researchers discovered that those with a history of HSV-1 were 80% more likely to develop Alzheimer’s than those who did not.
Furthermore, individuals who received antiviral treatment for HSV-1 had about 17% lower risk of Alzheimer’s disease than those who did not receive treatment.
Previous studies have also linked HSV-1 and Alzheimer’s
The involvement of viruses in Alzheimer’s is not a new concept; scientists have previously hypothesized that viruses may play a part in the disease. Previous studies have found HSV-1 DNA in postmortem brain tissues from Alzheimer’s patients [3, 7].
Laboratory studies have shown that HSV-1 can lead to the accumulation of amyloid-beta plaques in the brains and nerve cells of animals [8]. Since amyloid-beta plaques are one of the hallmarks of Alzheimer’s disease pathology, there has been conjecture that virus reactivation could be a factor in brain damage or inflammation.
However, earlier research and the current study demonstrate connections rather than proof that HSV-1 causes Alzheimer’s. These connections don’t prove the virus causes or accelerates the course of the illness.
What are the limitations of the study?
The study’s retrospective nature, inability to confirm Alzheimer’s diagnoses, and failure to ascertain crucial information on the used antiherpes drugs (like dosage and duration) were some of its limitations. However, the results are consistent with prior research that linked herpes viruses to Alzheimer’s disease. More research is required to establish the cause and may ultimately determine whether antiviral treatments are a successful treatment for dementia.
The study included information from insurance claims, which may not always represent timely or precise clinical diagnosis. Additionally, HSV-1 is commonly underdiagnosed, particularly in cases when symptoms are mild or nonexistent. These factors may help to explain why, despite estimates of much greater population rates of HSV-1, both the Alzheimer’s group and the control group experienced such low levels of the virus.
This suggests that many HSV-1 carriers in the study may have gone undetected, making the link more challenging to evaluate. The dataset also does not include information on how frequently participants experienced recurring symptoms, as well as the intensity or length of illnesses, all of which may have a direct impact on risk.
People with HSV-1 may differ from those without it in other ways, which is another problematic factor. Risk factors for Alzheimer’s may include lifestyle, genetics, immune system health, education, and differences in access to healthcare.
Should you worry if you have cold sores?
In short, no, at least not according to the facts available today. The majority of HSV-1 carriers will never have Alzheimer’s. Most people who have the virus do not experience any severe neurological problems.
Although it is not yet a proven theory, the “herpes hypothesis” of Alzheimer’s disease is an intriguing topic for further study. This study contributes to the topic but does not provide a conclusive answer.
Numerous risk factors, including age, genetics, heart health, education, lifestyle, and environmental exposures, contribute to the complexity of Alzheimer’s disease.
Infections such as HSV-1 may contribute to the risk factors, but they are very unlikely to be the only cause.
Alzheimer’s Research Association is a non-profit organization dedicated to helping caregivers of Alzheimer’s disease and dementia. We provide the latest information and news about the illness and helpful tips to help caregivers cope with their daily caregiving challenges. We realize the most important thing that a caregiver needs is financial assistance. Therefore, we provide grants to caregivers to ease their financial burden. Caregivers can apply for grants here: Alzheimer’s Grant Application.
You can also help caregivers in their endeavor by donating as much as possible: Donation To Alzheimer’s Research Associations.
References
- Alzheimer’s Disease Facts and Figures. Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/facts-figures. Accessed: 10th June, 2025.
- Wong, W., 2020. Economic burden of Alzheimer disease and managed care considerations. The American journal of managed care, 26(8 Suppl), pp.S177-S183.
- Itzhaki, R.F., Lin, W.R., Shang, D., Wilcock, G.K., Faragher, B. and Jamieson, G.A., 1997. Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. The Lancet, 349(9047), pp.241-244.
- Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F. and Zhang, C., 2024. Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway. Journal of Neuroinflammation, 21(1), p.176.
- Liu, Y., Johnston, C., Jarousse, N., Fletcher, S.P. and Iqbal, S., 2025. Association between herpes simplex virus type 1 and the risk of Alzheimer’s disease: a retrospective case–control study. BMJ open, 15(5), p.e093946.
- Herpes Simplex Virus. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus. Updated Online: 30th May, 2025. Accessed: 10th June, 2025.
- Jamieson, G.A., Maitland, N.J., Wilcock, G.K., Craske, J. and Itzhaki, R.F., 1991. Latent herpes simplex virus type 1 in normal and Alzheimer’s disease brains. Journal of medical virology, 33(4), pp.224-227.
- Eimer, W.A., Kumar, D.K.V., Shanmugam, N.K.N., Rodriguez, A.S., Mitchell, T., Washicosky, K.J., György, B., Breakefield, X.O., Tanzi, R.E. and Moir, R.D., 2018. Alzheimer’s disease-associated β-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron, 99(1), pp.56-63.
- Smith, R. Cold Sore Virus Linked to Higher Alzheimer’s Risk. Technology Networks. https://www.technologynetworks.com/immunology/news/cold-sore-virus-linked-to-higher-alzheimers-risk-399925. Published Online: 20th May, 2025. Accessed: 10th June, 2025.
- McClure, P. Anti-herpes medication use linked to 17% reduced risk of Alzheimer’s. https://newatlas.com/brain/alzheimers-dementia/herpes-simplex-1-alzheimers-risk-antiviral-medication/. Published Online: 20th May, 2025. Accessed: 10th June, 2025.
- Cold Sore Virus Linked to Alzheimer’s, Antivirals May Lower Risk. Neuroscience News. https://neurosciencenews.com/hsv-1-antiviral-alzheimers-28994/. Published Online: 21st May, 2025. Accessed: 10th June, 2025.
- Siette, J. Could cold sores increase the risk of Alzheimer’s disease? A new study is no cause for panic. The Conversation. https://theconversation.com/could-cold-sores-increase-the-risk-of-alzheimers-disease-a-new-study-is-no-cause-for-panic-257140. Published Online: 22nd May, 2025. Accessed: 10th June, 2025.
